Acute EPA-induced learning and memory impairment in mice is prevented by DHA

被引：54

作者：

Liu, Ji-Hong ^{[1
]}

Wang, Qian ^{[1
]}

You, Qiang-Long ^{[1
]}

Li, Ze-Lin ^{[1
]}

Hu, Neng-Yuan ^{[1
]}

Wang, Yan ^{[2
,3
]}

Jin, Zeng-Lin ^{[4
]}

Li, Shu-Ji ^{[1
]}

Li, Xiao-Wen ^{[1
]}

Yang, Jian-Ming ^{[1
]}

Zhu, Xin-Hong ^{[1
]}

Dai, Yi-Fan ^{[2
,3
]}

Xu, Jiang-Ping ^{[5
]}

Bai, Xiao-Chun ^{[6
]}

Gao, Tian-Ming ^{[1
]}

机构：

[1] Southern Med Univ, State Key Lab Organ Failure Res,Dept Neurobiol,Sc, Key Lab Mental Hlth,Guangdong Prov Key Lab Psychi, Minist Educ,Guangdong Hong Kong Macao Greater Bay, Guangzhou 510515, Peoples R China

[2] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 210029, Peoples R China

[3] Nanjing Med Univ, Jiangsu Key Lab Xenotransplantat, Nanjing 210029, Peoples R China

[4] Beijing Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China

[5] Southern Med Univ, Sch Pharmaceut Sci, Dept Pharmacol, Guangzhou 510515, Peoples R China

[6] Southern Med Univ, Sch Basic Med Sci, Dept Cell Biol, Guangzhou 510515, Peoples R China

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

POLYUNSATURATED FATTY-ACIDS; LONG-TERM POTENTIATION; 5-HT6 RECEPTOR ANTAGONISTS; AGE-RELATED-CHANGES; DOCOSAHEXAENOIC ACID; EICOSAPENTAENOIC ACID; DOUBLE-BLIND; ETHYL-EICOSAPENTAENOATE; COGNITIVE FUNCTION; ALZHEIMER-DISEASE;

D O I：

10.1038/s41467-020-19255-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Eicosapentaenoic acid (EPA), an omega-3 fatty acid, has been widely used to prevent cardiovascular disease (CVD) and treat brain diseases alone or in combination with docosahexaenoic acid (DHA). However, the impact of EPA and DHA supplementation on normal cognitive function and the molecular targets of EPA and DHA are still unknown. We show that acute administration of EPA impairs learning and memory and hippocampal LTP in adult and prepubescent mice. Similar deficits are duplicated by endogenously elevating EPA in the hippocampus in the transgenic fat-1 mouse. Furthermore, the damaging effects of EPA are mediated through enhancing GABAergic transmission via the 5-HT6R. Interestingly, DHA can prevent EPA-induced impairments at a ratio of EPA to DHA similar to that in marine fish oil via the 5-HT2CR. We conclude that EPA exhibits an unexpected detrimental impact on cognitive functions, suggesting that caution must be exercised in omega-3 fatty acid supplementation and the combination of EPA and DHA at a natural ratio is critical for learning and memory and synaptic plasticity. Acute administration of EPA impairs learning and memory and hippocampal LTP in mice that was mediated through enhancing GABAergic transmission via the 5-HT6R. DHA can prevent EPA-induced impairments at a ratio of EPA to DHA similar to that in marine fish oil via the 5-HT2CR.

引用

页数：15

共 83 条

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